Friday, November 30, 2012

Something smells fishy here

Mark Rotenberg, the General Counsel for the U, has repeatedly claimed that the U was investigated and cleared of blame in the Dan Markingson case by the Minnesota Attorney General's office, but he has never provided evidence for the claim.  If Rotenberg is speaking truthfully, how do we explain this letter to Mary Weiss in 2005?  In that letter, Deputy Attorney General Michael Vanselow expresses his pleasure that Mary has found legal counsel to represent her, and he also states his willingness to work with her and Jim Gottstein to draft legislation addressing the systemic problems that contributed to Dan's death.  (Those efforts eventually resulted in "Dan's Law," which prohibits Minnesota psychiatrists from recruiting patients into psychiatric drug studies if, like Dan, they are under a commitment order.)

How to file a complaint about the CAFE or CATIE studies to the Minnesota Board of Social Work


Anyone who is considering the possibility of filing a complaint to the Minnesota Board of Social Work about Jean Kenney, the study coordinator for the CAFE and CATIE studies at the University of Minnesota, might want to look at Mike Howard's complaint about Kenney, which resulted in a "corrective action" two weeks ago.

Wednesday, November 28, 2012

Psychiatric experiments on Hmong refugees



Many research scandals involve deception.  And some scandals, such as the one at the Jewish Chronic Disease Hospital, include the administration of dangerous substances.  Still others involve outright racism, such as the Tuskegee syphilis study.  But it is a rare scandal that involves all three.  In the early 1990s, the University of Minnesota’s Department of Psychiatry hit the trifecta. 
 
In 1993, when the University of Minnesota was under fire for covering up research fraud by Dr. Barry Garfinkel, the university found itself with yet another psychiatric scandal.  Dr. James Halikas, a tenured professor in the Department of Psychiatry, had gotten permission from the FDA to test a drug called gamma hydroxybutyrate, or GHB, for opiate addiction.  He began by recruiting uneducated Hmong refugees who did not speak English.  The Hmong patients had become addicted to opium in Laos, where the drug is often used as a painkiller. Although they had come to the university to get methadone maintenance treatment, the patients had discovered that the methadone clinic was closed to them.  Why?  Because Halikas had decided that Southeast Asians were taking up too many spots at the clinic.  He was only admitting non-Asians. 

Instead, according to the FDA, Halikas enrolled ten of those Hmong patients in his GHB study.  Although they complained bitterly that GHB didn’t work and repeatedly asked for methadone, it was not until a formal complaint was lodged by another faculty member, Dr. Sheila Specker, that an investigation was triggered.  It soon became clear that Halikas had never actually obtained informed consent from his subjects.  In fact, it is not even clear that the subjects even knew they were in a research study.  (This was not because Halikas didn’t know better; he was a member of the university’s Institutional Review Board.)  According to a later investigation by the FDA, several of the subjects were severely depressed and at risk of suicide, and should have never been enrolled in the study, even if they had given their consent.  Although Halikas told the Star Tribune that GHB is “so mild that it has been used in Europe as a children's sedative,” it is in fact a central nervous system depressant that is sometimes used as a date rape drug.  At the time of the study it had been linked to seizures and coma.  The FDA found that Halikas had dispensed it in dangerously high doses.

According to the Star Tribune, although the university investigated the complaint about Halikas, it did not inform state licensing officials who have jurisdiction over the drug program.  Nor did it bar Halikas from conducting research.  That did not happen until 2000, when the FDA formally “disqualified” him as a clinical researcher.

Forget the scandals, bring on the hype

More device industry PR in the Strib.  Am I sensing a pattern here?

Addendum: Gary Schwitzer weighs in again on the issue here.  (Scroll to the bottom.)

How to fool people with clinical trials

Read all about it.

Tuesday, November 27, 2012

Monday, November 26, 2012

For the University of Minnesota’s Department of Psychiatry, it’s déjà vu all over again




The recent research scandals out of the Department of Psychiatry may be alarming, but they are not new.  Back in the 1990s, when the university was working its way towards a crippling probation by the National Institutes of Health, the Department of Psychiatry hosted two spectacular episodes of research wrongdoing, both of which resulted in faculty members being debarred from conducting research by the FDA.

The first was the case of Dr. Barry Garfinkel, the head of Child and Adolescent Psychiatry. Garfinkel was the principal investigator for a $250,000 Ciba-Geigy study of Anafranil, an antidepressant, to determine if the drug was effective for obsessive-compulsive disorder in adolescents. Unfortunately, Garfinkel was not the most scrupulous researcher.  According to newspaper reports, Garfinkel falsified data, submitted forms for psychiatric evaluations that didn’t actually take place, and instructed his research assistant to give therapy to subjects even though she had no medical training.  For this Garfinkel wound up in federal court, where he was sentenced to six months in federal prison, six months of home detention, 400 hours of community service, and was fined $214,000.

Sound familiar?  It gets better.  Even more impressive than Garfinkel’s fraud were the actions taken by University of Minnesota administrators to protect him.  After the whistleblower that alerted the university was fired, the Dean of the Medical School, David Brown, made a secret agreement with Garfinkel to keep the university investigation hidden for nearly four years.  The university spent nearly $180,000 in legal fees to maintain that secrecy.  When the FDA got involved, the university refused to share its findings until the FDA had them subpoenaed. The university later claimed in a press release that it had cooperated with the FDA – a claim that an FDA official told the Star Tribune he found “offensive.”  He said, "This is not what I would characterize as cooperation."

You can find newspaper coverage of the Garfinkel case here.  Coming up next: the case of James Halikas.

More home cooking from the Star Tribune

Gary Schwitzer wonders again why the Strib has become so friendly to the local device industry.

Community Alliance for Ethics in Minnesota Psychiatry

I have started a new Facebook group aimed especially at Minnesotans concerned with recent developments in psychiatric care and research in the state.  It is called Community Alliance for Ethics in Minnesota Psychiatry, and can be found here:

https://www.facebook.com/pages/Community-Alliance-for-Ethics-in-Minnesota-Psychiatry/377132245708063

I hope for this page to become a resource for psychiatric patients, research subjects and their families in the state, especially those who have had difficulties with the mental health system.

Carl Elliott


Friday, November 23, 2012

A reporter's guide to the Dan Markingson case

For anyone unfamiliar with the death of Dan Markingson in the CAFE study at the University of Minnesota, a brief summary can be found here, followed by a more detailed explanation with links to source documents.

Wednesday, November 21, 2012

Why research subjects in the CATIE study should be alarmed

The suicide of Dan Markingson at the University of Minnesota has brought notoriety to the CAFÉ study and its site investigators, Stephen Olson and Charles Schulz.  But the “corrective action” recently issued by the Minnesota Board of Social Work against the CAFÉ study coordinator, Jean Kenney, has raised another disturbing question.  Kenney was not just the study coordinator for the CAFÉ study; she also worked on the CATIE study.  Kenney’s ethical violations in the CAFÉ study were extensive and alarming.  Did they occur in the CATIE study as well?

Like the CAFÉ study, the CATIE study compared several atypical antipsychotics in the treatment of patients with schizophrenia.  Olson was the University of Minnesota site investigator for both studies.  Unlike the CAFÉ study, however, the CATIE study has been enormously influential.  By 2011, according to Jeffrey Lieberman, it had been cited in the medical literature over 1600 times. And unlike the CAFÉ study, which was sponsored by AstraZeneca, the CATIE study was backed by federal dollars.  It was funded by the NIMH and enrolled nearly 1500 subjects. If wrongdoing were discovered in the CATIE study, the consequences could be far-reaching.

According to the Board of Social Work, Kenney had responsibility for administering prescription drugs to research subjects and assessing their side-effects – including potentially life-threatening effects such as akathisia – despite the fact that she had no medical training.  She made significant mistakes about a medical diagnosis and medication dosage, and she apparently forged the initials of a physician on the medical chart.  When Markingson’s mother, Mary Weiss, left “alarming voicemail messages” warning that her son might commit suicide, Kenney failed to respond adequately.

Perhaps most significantly, when AstraZeneca and the CAFÉ study sponsors issued a safety alert about the risks of diabetes and hyperglycemia for patients taking Seroquel, Kenney failed to inform research subjects.  In fact, the principal investigator for the University of Minnesota site, Stephen Olson, did not even ask the IRB to approve a revised consent form until May 10, 2004 – over four months after the first safety alert was issued.  As the Board of Social Work pointed out, the failure to inform a research subject of these new risks would effectively invalidate that subject’s original informed consent.

Did Kenney and Olson also fail to inform research subjects in the CATIE study of these new risks?  The safety alerts for Zyprexa and Risperdal – which, like Seroquel, were study drugs in the CATIE study – were issued in March and August 2004, respectively. The CATIE study would have still been going on during that period.

If officials at the University of Minnesota were genuinely concerned about protecting research subjects in clinical trials, it would take the Kenney “corrective action” as a reason to look into the conduct of the CATIE study.  Given their reaction to the Markingson case, there is no reason to think that will happen.  However, if you or anyone you know was a subject in the CATIE study (or the CAFÉ study) and would like to talk to someone about your concerns, please feel free to get in touch with me.

Monday, November 19, 2012

Fact-checking the General Counsel at the University of Minnesota

Ever since critics began asking questions about the death of Dan Markinson in a clinical trial at the University of Minnesota, the General Counsel for the university, Mark Rotenberg, has responded with a uniform message: the case has already been investigated many times, and no wrongdoing has ever been found. That's how Rotenberg responded to my article about the case in Mother Jones, and that's how he responded last week to the news that the Board of Social Work had issued a “corrective action” to the study coordinator for the clinical trial in which Markingson died. Rotenberg told City Pages:

“The FDA, the Hennepin County District Court, the Minnesota Board of Medical Practice, the Minnesota Attorney General's Office and the University's Institutional Review Board have all reviewed the case. None found fault with any of our faculty. Most importantly, none found any causal link between the CAFE trial and the death of Mr. Markingson."

This is a deeply problematic statement, but it has been repeated so many times that reporters appear to believe it.

First, to say that the university's Institutional Review Board reviewed the case and found no fault is highly misleading. The IRB is the university body charged with protecting subjects in university research studies. It reviews all studies that are done at the university. Its mistakes in overseeing the CAFE study are part of what is at issue in this case.

Second, I have never been able to verify Rotenberg's claim that the Minnesota Attorney General's office reviewed the Markingson case and found no fault. No report from the Attorney General's office appeared in the documents associated with the lawsuit by Mary Weiss, nor to my knowledge has it appeared in any other publicly available material. If there was such a review, and if it indeed found no fault with university faculty members, it needs to be squared with the “agreement for corrective action” for Jean Kenney, which apparently did involve the Attorney General's Office, and which came to a very different conclusion.  According to that document (see page 8) the Board of Social Work panel was represented by Assistant Attorney General Benjamin R. Garbe.

Third, it is wrong to claim that the Hennepin County District Court reviewed the case and found no fault with university faculty members. In the lawsuit brought by Mary Weiss in Hennepin County District Court, a judge ruled in a partial summary judgment that the university IRB was “statutorily immune from liability.” As Matt Lamkin at Stanford Law School told me, to suggest that the University of Minnesota was exonerated in this lawsuit is like a diplomat who got drunk and ran over a kid claiming he was "exonerated" by diplomatic immunity.

As for the decisions of the Minnesota Board of Medical Practice: we'll never know what the Board decided, because its files are closed. (It is probably worth noting, however, that the Board consistently disciplines fewer doctors per capita than nearly any other state in the country.) The only review that is publicly available is a report by the FDA – a deeply flawed investigation that I have written critically about in the Hastings Center Bioethics Forum.




What did it cost to defend sanctioned social worker in the Markingson case?

The University of Minnesota paid "a portion" of Jean Kenney's legal bills in her case with the Minnesota Board of Social Work, according to today's City PagesA data practice request has revealed that university paid  $18,909 for Kenney's attorney, and $3,864 to Dr. Frederic Reamer of Rhode Island College for expert testimony on Kenney's behalf.  That comes to a total of $22,773.

For a complaint that was filed over 3 1/2 years ago, these figures seem remarkably low.  The question now is: exactly what portion of Kenney's legal bills did the university pay, and who paid for the rest?

Thursday, November 15, 2012

The University of Minnesota was not involved? Some further thoughts on the “corrective action” against Jean Kenney in the Markingson case

The “corrective action” against Jean Kenney, the study coordinator in the clinical trial in which Dan Markingson committed suicide, has sparked new attention to the case.  I posted my initial reaction to the action on Monday; here are some further thoughts.

First, in statements to the press, the General Counsel for the University, Mark Rotenberg, appears to claim that the University of Minnesota was not involved in the deliberations about Kenney.  In a statement to Pharmalot, Rotenberg says that Kenney “hasn’t been employed by U of M for years and we were not a party to the proceeding.”  To City Pages, Rotenberg said, “The University was not a party in the Corrective Action.”  The idea that the university was not involved in this case seems highly implausible.  Kenney was defended by the same law firm that defended the University of Minnesota in the lawsuit brought by Mary Weiss, and her spokesperson in the affair has been David Alsop, the attorney who defended the university.  Asked by Pharmalot whether the university paid Kenney’s legal fees, Rotenberg said that the university “may have made a fee arrangement with her.”  (“May have”?  Does this mean Rotenberg doesn’t actually know if the university paid Kenney’s legal fees?)

Second, while the “corrective action” lists a number of alarming problems with Kenney’s work, it does not mention most of the most egregious ethical wrongdoing in the case of Dan Markingson – the fact that he was coerced into the trial over the objections of his mother while under a commitment order, his questionable capacity to give informed consent, the conflicts of interest of the investigators, the financial incentives to enroll Markingson in the study, the dubious scientific value of the CAFE study, to name just a few.  These omissions can’t be because Kenney was not involved in these matters.  For example, Kenney was the person charged with assessing Markingson’s competence to consent.

Third, Mike Howard and Mary Weiss also filed a complaint about Stephen Olson, Kenney’s supervisor in the CAFÉ study, to the Minnesota Board of Medical Practice.  Yet unlike the Board of Social Work, the Board of Medical Practice took no action.  Why not?  The wording of the “corrective action” by the Board of Social Work suggests that Kenney was simply following the orders of her superiors.

Fourth, Rotenberg says the findings by the Board of Social Work will not change the university’s stance toward the CAFÉ study.  According to Pharmalot, Rotenberg says “the university does not feel obligated to reopen its investigation into the handling of the CAFE trial.”  If this is so, it would be a serious mistake.  According to the deposition of Stephen Olson, Markingson was only one of seventeen subjects enrolled by the University of Minnesota in the CAFÉ study.  If Kenney made this many mistakes with Markingson, it stands to reason that her mistakes would very likely extend to the other subjects in the study.  In addition, Kenney was also the study coordinator for the AstraZeneca CLEAR study, and more importantly, the National Institutes of Mental Health CATIE study.  If University of Minnesota administrators were genuinely interested in getting to the bottom of these problems, would they not want to look further?

Carl Elliott

Wednesday, November 14, 2012

"Do we have to wait until he kills himself or someone else before anyone else does anything?"



In the "agreement for corrective action" against CAFE study coordinator Jean Kenney last week, the Board of Social Work cited Kenney's failure to respond to "alarming voicemail messages" from family members of Dan Markingson. Presumably, the Board is referring to a message left by his mother, Mary Weiss, which warned, "Do we have to wait until he kills himself or someone else before anyone else does anything?"  The failure of Kenney and Stephen Olson to take the warnings of Mary Weiss seriously has been one of the most disturbing aspects of this case.  In a deposition for the lawsuit filed by Weiss, Kenney was questioned about her response.  Here is an excerpt.  (The initial questions come from Gale Pearson, an attorney for Mary Weiss.)

BY MS. PEARSON:

Q. What was your first impression after you heard this telephone message from Mrs. Weiss?

A. I remember her -- she's obviously very upset, I guess. You know, I didn't have any details about why she thought his meds weren't working. The statement, "Are you asking me or telling me," didn't really tell me much. I didn't quite understand that. And when she said, "Do we have to wait until he kills himself or someone else?" I guess I really wanted to know more about why she was making that -- why she was so concerned about that, because I just remember thinking at the time, you know, we weren't seeing anything like that, and the group home wasn't seeing anything like that and his case manager wasn't seeing anything like that and the treatment program wasn't seeing anything like that, so I wanted to know more from her because she was obviously very concerned.

Q. What did you do to find out more from her?
 
A. I remember there was a series of phone calls and that we really wanted Mary to come in to talk about that, because certainly her concerns needed to be heard.

Q. Who were those series of phone calls to?

A. Back and forth to Mary, I guess.

Q. Between -- I'm sorry, I didn't mean to interrupt you. Between who and who?

A. Myself and Mary, that I'm aware.

Q. Did you notify Dr. Olson about this statement in the record?

A. Sure.

Q. What did Dr. Olson say?

A. I don't remember specifically what he said. I do know anytime I ever expressed concerns, he wanted me to follow up on it, and I think, if I remember correctly, at that time we wanted to, you know, find out from Dan what was going on and also to check out from the other places what they were seeing as well, too, and we have to kind of gather information from everybody.

Q. What did Dr. Olson do after he heard this report from you that his mother was concerned that her son might kill himself?

MR. HUTCHINSON: Objection, lack of foundation, but go ahead.

THE WITNESS: You know, I don't remember specifically what he did.

BY MS. PEARSON:

Q. Did he do nothing?

A. No. I mean, we talked about things. I think we probably talked about when would Dan's next visit be, when -- you know, I should probably call the group home and find out what's going on, which I believe I did.

Q. Did you report this complaint to the IRB?

A. No, I don't believe I did report that mom said that, no.

Q. Why?

A. I don't know. I don't think I had any indication that that was something that I needed to report. It wasn't a -- I'm not seeing that that would be like an adverse event to report.

Q. Do you know whether or not the IRB is interested in hearing complaints regarding their clinical subjects in the trials that they're overseeing?

MR. ALSOP: That's a misstatement of the evidence here. I'll object, but go ahead.

MR. HUTCHINSON: Same. Lack of foundation, but go ahead.

THE WITNESS: I guess I don't know the answer if I would be the one responsible to report complaints to IRB.

BY MS. PEARSON:

Q. So you're saying there is no policy in place from the University of Minnesota's IRB that would direct a response from you after hearing something like this from the mother of a clinical trial subject?

A. I don't know if there's a policy or not on that. I really don't.

Q. But you don't know of one, as you sit here today, correct?

A. I don't know. I would be making a guess if I said that I know with certainty. I don't know.

Q. But you can't recall at this moment that there is a policy that would direct you to report this type of  complaint to the IRB?

MR. ALSOP: Same objections.

A.I don't know if there is a policy like that to report this.

Q. Do you know whether or not Dr. Olson reported this complaint --

A. I don't know if he did.

Q. -- to the IRB?

A. I don't know that he did report this specific complaint to the IRB.

Q. Would there have been anything that would have prevented you from going to the IRB with this clinical trial subject's concern?

A. No. Like being told, "Don't tell IRB this" or --

Q. Uh-huh.

A. No.

Q. So it would have been something you could have easily gotten on the phone and told the IRB and said, "Guess what? We've got some concerns here. We don't know what to do. We just wanted to notify you just to alert you there are some concerns."

MR. HUTCHINSON: Just a second, the "we don't know what to do" part of that is assuming facts not in evidence, lacking foundation, calling for speculation and conjecture. Go ahead.

THE WITNESS: Could you ask the question again.

BY MS. PEARSON:

Q. It could have been something you could have done. You could have gotten on the phone and said, "Look, we've got a complaint regarding one of our vulnerable adults" and you know, setting aside, I just want to clarify an understanding: You do understand that Daniel Markingson, under law, Minnesota law, is designated as a vulnerable adult. You do know that, correct?

MR. HUTCHINSON: Objection, lack of foundation. Go ahead.

THE WITNESS: I believe he would be considered a vulnerable adult.

BY MS. PEARSON:

Q. We've got a vulnerable adult whose mother is contacting the study coordinator complaining that  the medications in the study are not working and that she has concerns about the lack of response and she says to you, "Do we have to wait until he kills himself or someone else before anyone else does a thing?"

A. Uh-huh. Okay.

MR. HUTCHINSON: So --

THE WITNESS: Say the question again.

BY MS. PEARSON:

Q. So that's not something that you think ought to be reported to the IRB?

A. At that time, I did not think that was something I had to report to the IRB. I felt that that was something I had to report to Dr. Olson.

Q. And you did report it to Dr. Olson.

A. Yes.

Q. Did you report it to anybody else?

A. I don't remember.

Q. What else did you do in response to this concern expressed by Mrs. Weiss?

A. I remember --

MR. HUTCHINSON: You want her to -- other than what she wrote in her note, or you want her to repeat what's in the note or –

MS. PEARSON: I want to know if she did anything other than write it down and tell Dr. Olson.

MR. HUTCHINSON: Well, the writing described some of the things she did. That's why I'm asking the question. Do you want her to --

BY MS. PEARSON:

Q. Well, go ahead. You know, what else did you do?

A. I called the group home to find out what it was she was talking about.

Q. And what was that?

A. Oh, there was something about -- what I remember was that they went to pick him up for Easter and he didn't want to come or something like that and that's when he made the comment to, I believe it was the boyfriend, that, his fists were doubled and he said something about "I'm invisible." And then I called the group home to see what happened and they remembered saying well, they thought there was some kind of miscommunication about what time he was being picked up, et cetera, and I said to her, you know, "Are you having any concerns about Dan?" And she said, "No, he's fine here."

BY MS. PEARSON:

Q. And that satisfied you that you did not have to account any further on Mrs. Weiss' concerns that her son may kill himself.

MR. HUTCHINSON: That's not what she said. That's not what mom is reported to have said. I think she's asking if you did anything else after hearing that. Apparently that's what you're asking.

THE WITNESS: I don't remember what else I did.

BY MS. PEARSON:

Q. I guess I'm asking if the explanation from the Theo House satisfied you that there is nothing further to be concerned about after his mother calls and says, "Do we have to wait to kill himself or someone else before anyone does anything?"

A. No, I don't think that would satisfy me, because I believe that, you know, we have to listen to everything and continue. But in terms of making any decisions, I mean, we have to take it from everybody. How do I decide who to believe, one person over another? I mean --

Q. Who is right here, Jeanne -- Mrs. Kenney? I apologize. I apologize. Who was right here?

MR. HUTCHINSON: Well --

MS. SVITAK: I'm going to object, argumentative.

MR. HUTCHINSON: Just a second.

BY MS. PEARSON:

Q. What happened to Mr. Markingson before this study was completed?

A. I know what happened to him, but I don't know --

Q. I'm sorry. What happened to Mr. Markingson? Please answer the question.

A. Mr. Markingson killed himself.